Cited by 2,055Anesthesia and Neurotoxicity ResearchNeuroscience and Neuropharmacology ResearchCell death mechanisms and regulation

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Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain

Ikonomidou, Chrysanthy, Bosch, Friederike, Miksa, Michael, Bittigau, Petra, Vöckler, Jessica, Dikranian, Krikor, Tenkova, Tanya I., Stefovska, Vanya, Turski, Lechoslaw, Olney, John W.·1999·Science

DOI 10.1126/science.283.5398.70

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Abstract

Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N -methyl- d -aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.

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Authors: Ikonomidou, C., Bosch, F., Miksa, M., Bittigau, P., Vöckler, J., Dikranian, K., Tenkova, T. I., Stefovska, V., Turski, L., & Olney, J. W.
Affiliations: Washington University in St. Louis (US)
C. Ikonomidou, F. Bosch, M. Miksa, P. Bittigau, J. Vöckler, V. Stefovska, Department of Pediatric Neurology, Charité-Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. K. Dikranian, T. I. Tenkova, J. W. Olney, Department of Psychiatry, Washington University School of Medicine, 4940 Children's Place, St. Louis, MO 63110, USA. L. Turski, Eisai London Research Laboratories, Bernard Katz Building, University College London, Gower Street, London WC1E 6BT, UK.
Corresponding author: Ikonomidou, Chrysanthy
ORCID: Ikonomidou, Chrysanthy
Bittigau, Petra
Dikranian, Krikor
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1999-01
Volume: 283
Issue: 5398
Pages: 70-74
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.283.5398.70
OpenAlex: W2036650593
Cited by: 2,055
References: 33
Citations by year: 2026: 17 · 2025: 36 · 2024: 41 · 2023: 43 · 2022: 49 · 2021: 73 · 2020: 63 · 2019: 148 · 2018: 85 · 2017: 86 · 2016: 112 · 2015: 98 · 2014: 94 · 2013: 92 · 2012: 92
FWCI: 13.19
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5k05mh038894-20)
National Institute on Aging (AG11355, P01AG011355)
National Institute of Mental Health (MH-38894)
National Institute on Drug Abuse (R01DA005072, DA05072)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: NMDA receptor blockade, apoptosis, neuronal survival, glutamate excitotoxicity, brain development, fetal brain development, neonatal brain development, neurodevelopmental disorders, prenatal drug exposure, pediatric anesthesia, excitatory neurotransmitter
MeSH terms: Animals, Brain, Calcium Channel Blockers, Dose-Response Relationship, Drug, Fetus, Haloperidol, Immunohistochemistry, Microscopy, Electron, Nerve Degeneration, Neurons, Quinoxalines, Scopolamine, Receptors, N-Methyl-D-Aspartate, Dizocilpine Maleate, Apoptosis, Dopamine Antagonists, Excitatory Amino Acid Antagonists, Muscarinic Antagonists, In Situ Nick-End Labeling, Rats

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Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain

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